An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Non-Hodgkins Lymphoma
About this trial
This is an interventional treatment trial for Non-Hodgkins Lymphoma
Eligibility Criteria
Main Inclusion Criteria
- Histologically-confirmed hematologic malignancy that is expected to express CD20 (Relapsed after or refractory to respond to at least one prior treatment regimen; no available treatment options that are expected to prolong survival or patients refusing chemotherapy or autologous stem cell transplant (SCT). Note: The expansion part is restricted to relapsed/refractory follicular lymphoma (r/r FL) and relapsed/refractory diffuse large B cell lymphoma (r/r DLBCL))
- At least one measurable target lesion
- Fresh pre-treatment biopsy, but if this cannot be taken, a previous archived biopsy from metastatic lesion can be taken as replacement if it is not older than 6 months and not confounded by major events (progression, treatment)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate organ function (liver, hematological, renal)
- Negative test results for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV)
Inclusion Criteria Specific to Imaging Substudy
- At least two measurable target lesions
- Able to provide two fresh tumor biopsies (baseline and on-treatment)
Main Exclusion Criteria
- Participants with Chronic Lymphocytic Leukemia (CLL), acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, Richter's transformation, CD20-positive ALL, Burkitt lymphoma, or lymphoplasmacytic lymphoma
- Current > Grade 1 peripheral neuropathy (only for participants being treated in the polatuzumab vedotin arm)
- Patients with known active infection, or reactivation of a latent infection within 4 weeks prior to Obinutuzumab (Gpt) infusion
- Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
- History of leptomeningeal disease
- Current or past history of central nervous system (CNS) lymphoma
- Current or past history of CNS disease
- Major surgery or significant traumatic injury </=28 days prior to Gpt infusion
- Significant cardiovascular disease or significant pulmonary disease
- Active or history of autoimmune disease or immune deficiency (with exceptions, e.g. hypothyroidism and Diabetes mellitus Type 1)
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Treatment with any other standard anti-cancer radiotherapy / chemotherapy including investigational therapy within 4 weeks prior to Gpt infusion
- Prior solid organ transplantation
- Prior allogenic stem cell transplant (SCT)
- Autologous SCT within 100 days prior to Gpt infusion
- Documented refractoriness to an obinutuzumab-monotherapy regimen
- Prior treatment with anti-cancer/lymphoma therapies and systemic immunotherapeutic/immunostimulating agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to Gpt infusion
- Any history of immune related >/= Grade 3 adverse events (AE) with the exception of endocrinopathy managed with replacement therapy
- Ongoing corticosteroid use >25 milligrams/day of prednisone or equivalent within 4 weeks prior to and during study treatment
- Treatment with systemic immunosuppressive medication
- Administration of a live, attenuated vaccine within 4 weeks prior to Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment
Exclusion Criteria Specific to Imaging Substudy
- Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count and/or the presence of abnormal/malignant cells in the peripheral blood differential signifying circulating lymphoma cell
- Participants who have had splenectomy or functional asplenia that could compromise protocol objectives
Sites / Locations
- Novant Health Cancer Institute
- Ohio State University; Clinical Investigations Office
- UZ Gent
- Aarhus Universitetshospital Skejby; BlodsygdommeRecruiting
- Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KATRecruiting
- Odense Universitetshospital; Hæmatologisk AfdelingRecruiting
- Hadassah Ein Karem Hospital; HaematologyRecruiting
- Rabin Medical Center-Beilinson Campus;Hematology-OncologyRecruiting
- Chaim Sheba Medical Center; Department of HematologyRecruiting
- Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
- Policlinico S.Orsola-Malpighi;Istituto di Ematologia "Seragnoli"
- ASST PAPA GIOVANNI XXIII; EmatologiaRecruiting
- Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia
- Hospital Universitari Vall d'Hebron; Servicio de HematologiaRecruiting
- Hospital Duran i Reynals; Servicio de Hematologia
- START Madrid-FJD, Hospital Fundacion Jimenez DiazRecruiting
- HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio HematologiaRecruiting
- Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
- Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
- The HOPE Clinical Trials Unit
- University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility
- The Newcastle upon Tyne Hospitals NHS Foundation TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Atezolizumab
Polatuzumab Vedotin
Imaging Sub-study
Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD).
Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.
Participants will undergo positive-emission tomography/computed tomography (PET/CT) at screening, followed by an "Imaging Cycle," to replace Cycle 1 of the main study. Eligible participants will have the option roll-over to the atezolizumab arm of the main study from Cycle 2 onwards.